Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Newly discovered ’branding’ process helps immune system cells pick their fights

18.05.2005


Finding may have ramifications for vaccines, autoimmunity and atherosclerosis



Scientists have uncovered a new method the immune system uses to label foreign invaders as targets to be attacked. Researchers showed that the immune system can brand foreign proteins by chemically modifying their structure, and that these modifications increased the chances that cells known as lymphocytes would recognize the trespassers and attack them. "Now that we know that some T cells need to see these types of modifications to identify an invader, we can see if incorporating such changes into the proteins is helpful for vaccination," says senior author Emil R. Unanue, M.D., the Edward Mallinckrodt Professor and head of Pathology and Immunology.

The finding may also be relevant to autoimmune conditions where the immune system erroneously attacks healthy tissues. Such disorders include rheumatoid arthritis, multiple sclerosis and type 1 diabetes. "We show in this study that during some infections, these same types of modifications can be made to our own proteins, potentially leading to T cell attacks on the self," says Unanue.


Unanue and colleagues, who publish their results on May 31 in the Proceedings of the National Academy of the Sciences, conducted their studies in mice and in cultures of mouse cells. Jeremy Herzog, a research associate in Unanue’s lab, did many of the experiments and was the lead author of the study.

T cells belong to a class of immune cells known as thymic-lymphocytes, which in turn are a component of the branch of the immune system known as adaptive immunity. This branch responds to pathogens after they interact with the other major branch, the innate immune system. T cells kill pathogens or produce molecules like cytokines that stop their growth. Scientists have known for some time that a second class of innate immune system cells known as antigen-presenting cells helps T cells determine what to attack. They do this by displaying fragments of proteins they have picked up on their surfaces for inspection by T cells. Fragments of proteins are called peptides.

Researchers also knew that when antigen-presenting cells are activated by inflammatory factors or microbial products, they start putting out chemically unstable compounds such as nitric oxide and superoxide. Together, these compounds generate peroynitrate, a highly potent chemical that modifies many proteins.

Unanue’s group showed that this chemical modifies the peptides presented by antigen-presenting cells in several distinct ways. For example, they attach a nitrate group to the amino acid tyrosine in the peptides, changing it to nitrotyrosine. Unanue’s lab then showed that these changes increased the chances that various types of T cells would react to the modified peptides shown to them by antigen-presenting cells.

Unanue’s group is working to substantiate their findings and explore their potential relevance to different areas of biomedical research. He notes that insulin-producing beta cells, the pancreatic cells attacked by T cells in type 1 diabetes, also generate reactive compounds similar to those made by antigen-presenting cells. "The beta cells could therefore be modifying their own proteins in the same way that antigen-presenting cells are modifying foreign proteins," he says. "We’re now investigating whether such modifications can cause T cells to attack the beta cells."

Damaging oxidative reactions are also believed to play a role in atherosclerosis. Scientists suspect oxidative damage in the blood vessel walls may lead to immune reactivity that contributes to narrowing and stiffening of blood vessels.

Herzog J, Maekawa Y, Cirrito TP, Illian BS, Unanue ER. Activated antigen-presenting cells select and present chemically modified peptides recognized by unique CD4 T cells. Proceedings of the National Academy of the Sciences, 102 (22), 7928-7933.

Funding from the National Institutes of Health and the Kilo Diabetes and Vascular Research Foundation supported this research.

Washington University School of Medicine’s full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

Michael C. Purdy | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Life Sciences:

nachricht During HIV infection, antibody can block B cells from fighting pathogens
14.08.2018 | NIH/National Institute of Allergy and Infectious Diseases

nachricht First study on physical properties of giant cancer cells may inform new treatments
14.08.2018 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

Im Focus: World record: Fastest 3-D tomographic images at BESSY II

The quality of materials often depends on the manufacturing process. In casting and welding, for example, the rate at which melts solidify and the resulting microstructure of the alloy is important. With metallic foams as well, it depends on exactly how the foaming process takes place. To understand these processes fully requires fast sensing capability. The fastest 3D tomographic images to date have now been achieved at the BESSY II X-ray source operated by the Helmholtz-Zentrum Berlin.

Dr. Francisco Garcia-Moreno and his team have designed a turntable that rotates ultra-stably about its axis at a constant rotational speed. This really depends...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

'Building up' stretchable electronics to be as multipurpose as your smartphone

14.08.2018 | Information Technology

During HIV infection, antibody can block B cells from fighting pathogens

14.08.2018 | Life Sciences

First study on physical properties of giant cancer cells may inform new treatments

14.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>